Lamb-Shaffer syndrome in a Chinese adolescent: A case report

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Rare Diseases

Background:

• Lamb-Shaffer syndrome (LAMSHF) is a rare neurodevelopmental disorder caused by pathogenic variants in the SOX5 gene.
• The genotypic and phenotypic spectrum of LAMSHF is continually expanding with new variant discoveries.

Purpose of the Study:

• To report a novel SOX5 gene variant identified in a patient with clinical features consistent with LAMSHF.
• To emphasize the importance of genetic testing in diagnosing unexplained neurodevelopmental disorders.

Main Methods:

• Whole-exome sequencing was performed on a 15-year-old male presenting with short stature, intellectual disability, epilepsy, and congenital anomalies.
• A novel heterozygous SOX5 variant (c.1160G>A, p.Ser387Asn) was identified and correlated with the patient's phenotype.

Main Results:

• The identified SOX5 variant, initially of uncertain significance, supported the diagnosis of LAMSHF due to strong clinical correlation.
• The patient's epilepsy is managed with levetiracetam, and supportive care includes dental treatment and a recommended multidisciplinary rehabilitation approach.
• Seizures are controlled, and the patient shows stable cognitive and functional status.

Conclusions:

• This case highlights a novel SOX5 variant associated with LAMSHF.
• Genetic confirmation is vital for accurate diagnosis and management of patients with unexplained neurodevelopmental features.
• Early and accurate diagnosis can prevent unnecessary interventions.